Toll-like receptor 4 regulates early endothelial activation during ischemic acute kidney injury

Jianlin Chen, Reji John, James A. Richardson, John M. Shelton, Xin J. Zhou, Yanxia Wang, Qing Qing Wu, John R. Hartono, Pamela D. Winterberg, Christopher Y. Lu

Research output: Contribution to journalArticlepeer-review

121 Scopus citations


Ischemic acute kidney injury (AKI) triggers an inflammatory response which exacerbates injury that requires increased expression of endothelial adhesion molecules. To study this further, we used in situ hybridization, immunohistology, and isolated endothelial cells, and found increased Toll-like receptor 4 (TLR4) expression on endothelial cells of the vasa rectae of the inner stripe of the outer medulla of the kidney 4 h after reperfusion. This increase was probably due to reactive oxygen species, known to be generated early during ischemic AKI, because the addition of hydrogen peroxide increased TLR4 expression in MS1 microvascular endothelial cells in vitro. Endothelial TLR4 may regulate adhesion molecule (CD54 and CD62E) expression as they were increased on endothelia of wild-type but not TLR4 knockout mice in vivo. Further, the addition of high-mobility group protein B1, a TLR4 ligand released by injured cells, increased adhesion molecule expression on endothelia isolated from wild-type but not TLR4 knockout mice. TLR4 was localized to proximal tubules in the cortex and outer medulla after 24 h of reperfusion. Thus, at least two different cell types express TLR4, each of which contributes to renal injury by temporally different mechanisms during ischemic AKI.

Original languageEnglish (US)
Pages (from-to)288-299
Number of pages12
JournalKidney international
Issue number3
StatePublished - Feb 2011


  • acute kidney injury
  • endothelium
  • inflammation
  • ischemia-reperfusion

ASJC Scopus subject areas

  • Nephrology


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